Urinary System Infection
Urinary System Infection, in particular urinary tract infection, may be defined as the presence of microorganisms in the urinary tract that can not be accounted for by contamination. The organisms have the potential to invade the tissue of urinary tract and adjacent structures. Such infection may be limited to the growth of bacteria in the urine, which frequently may not produce symptoms. Urinary system infection may also present as several syndromes associated with an inflammatory response to microbial invasion and can range from asymptomatic bacteriuria to pyelonephritis with bacteremia or sepsis.
The microbiologic etiology of urinary system infections usually originates from bowel flora of the host. While virtually every organism has been associated with urinary system infections, certain organisms predominate as a result of specific virulence factors. The most common cause of uncomplicated urinary system infections is Escherichia coli, which accounts for almost 85% of community-acquired infections. Additional causative organisms in uncomplicated infections include Staphylococcus saprophyticus, Proteus sp., Klebsiella pneumonia, Pseudomonas aeruginosa, Enterococcus sp., and Staphylococcus epidermidis. 
In general, organisms gain entry into the urinary tract via three possible routes: the majority is the ascending, and the minority is the descending (hematogenous), and the very rare possibility, however no evidence, is the lymphatic pathway. The urine under normal circumstances is capable of inhibiting and killing microorganisms, the factors thought to be responsible include a low pH, extremes in osmolality, high urea concentration, high organic acid concentration, and in males the prostatic secretions.
Common Remedy for Urinary System Infection
In cases where treatment is needed for urinary system infections, antibiotics are commonly used.
Antibiotics kill (i.e. bacteriacide) or inhibit (i.e. bacteriastatic) the growth of microorganisms by interfering with specific biosynthesis or metabolism pathways inside the susceptible pathogens, thus depriving them of the metabolites essential to their survival.
The induction of resistance to antibiotic is a fate when the antibiotic is frequently and repeated used. It was shown that the susceptibility of E. coli to a certain antibiotic is inversely proportional to the time over which that particular antibiotic has historically been in use; this general trend holds despite some minor differences across antibiotics that may reflect their different frequencies of use.
Matrix Metalloproteinase & Cell Migration
Matrix metalloproteinases (MMPs) are a family of zinc- and calcium-dependent endopeptidases, which includes matrilysin, stromelysins, gelatinases, interstitial and neutrophil collagenases, collagenase-3 (MMP-13) and membrane-type MMPs. They digest different components of the extracellular matrix during physiologic and pathologic turnover (Tan, Y., Rouse, J., Zhang, A., Cariati, S., Cohen, P., Comb, M. J. FGF and stress regulate CREB and ATF-1 via a pathway involving p38 MAP kinase and MAPKAP kinase-2. EMBO J. 1996; 15: 4629-4642). The gelatinase-type matrix MMPs, MMP-2 and MMP-9, are capable of degrading type IV collagen in the basement membrane and thus are regarded as key enzymes in migration and invasion by several cell types, including macrophages, T cells and some tumour cells (Beyaert, R., Cuenda, A., Vanden, B. W., Plaisance, S., Lee, J. C., Haegeman, G., Cohen, P., Fiers, W. The p38/RK mitogen-activated protein kinase pathway regulates interleukin-6 synthesis in response to tumour necrosis factor. EMBO J. 1996; 15: 1914-1923; Suttles, J., Milhorn, D. M., Miller, R. W., Poe, J. C., Wahl, L. M., Stout, R. D. CD40 signaling of monocyte inflammatory cytokine synthesis through an ERK1/2-dependent pathway. A target of interleukin (IL)-4 and IL-10 anti-inflammatory action. J. Biol. Chem. 1999; 274: 5835-5842). Recently, constitutive secretion of MMP-9 and activation-induced secretion of MMP-2 have been shown to favour T-cell migration through a basement membrane in-vitro (Leppert, D., Waubant, E., Galardy, R., Bunnett, N. W., Hauser, S. L. T cell gelatinases mediate basement membrane transmigration in vitro. J. Immunol. 1995; 154: 4379-4389). Inhibition of T cell transmigration by interfering with the expression of these proteinases may represent a useful approach to the treatment of T-cell-mediated inflammation and autoimmune diseases.
Medical Uses of Matrix Metalloproteinase Inhibitors
Matrix metalloproteinases have been linked to cancers such as breast, ovarian, colorectal, and lung. Synthetic matrix metalloproteinase inhibitors are being explored for use in cancer prevention and treatment because of their demonstrated antimetastatic and antiangiogenic properties. Matrix metalloproteinase inhibitors include compounds such as: Marimastat (BB-2516), COL-3, BAY 12-9566, and KB-R7785. Marimastat (BB-2516) was the first orally bioavailable matrix metalloproteinase inhibitor to enter clinical trials in the field of oncology. Developing nontoxic, orally active, MMP inhibitors is important because these compounds will likely need chronic administration in combination with other therapies. However, MMP inhibitor was never used in terms of urinary system infection.